An overview of microRNAs

The discovery of the first microRNA (miRNA) over 20 years ago has ushered in a new era in molecular biology. There are now over 2000 miRNAs that have been discovered in humans and it is believed that they collectively regulate one third of the genes in the genome. miRNAs have been linked to many human diseases and are being pursued as clinical diagnostics and as therapeutic targets. This review presents an overview of the miRNA pathway, including biogenesis routes, biological roles, and clinical approaches

Resiliency for Entrepreneurs and Careerists

Resilience is a choice. Almost every case we studied of people who survived being lost in the wilderness said they “decided to survive. Even an eight-year-old boy lost overnight at 11,000 feet said, “I knew I wanted to live.”https://digitalcommons.usu.edu/huntsman_news/1192/thumbnail.jp

Echolocation detections and digital video surveys provide reliable estimates of the relative density of harbour porpoises

Acknowledgements We would like to thank Erik Rexstad and Rob Williams for useful reviews of this manuscript. The collection of visual and acoustic data was funded by the UK Department of Energy & Climate Change, the Scottish Government, Collaborative Offshore Wind Research into the Environment (COWRIE) and Oil & Gas UK. Digital aerial surveys were funded by Moray Offshore Renewables Ltd and additional funding for analysis of the combined datasets was provided by Marine Scotland. Collaboration between the University of Aberdeen and Marine Scotland was supported by MarCRF. We thank colleagues at the University of Aberdeen, Moray First Marine, NERI, Hi-Def Aerial Surveying Ltd and Ravenair for essential support in the field, particularly Tim Barton, Bill Ruck, Rasmus Nielson and Dave Rutter. Thanks also to Andy Webb, David Borchers, Len Thomas, Kelly McLeod, David L. Miller, Dinara Sadykova and Thomas Cornulier for advice on survey design and statistical approache. Data Accessibility Data are available from the Dryad Digital Repository: http://dx.doi.org/10.5061/dryad.cf04gPeer reviewedPublisher PD

Social Competence Treatment after Traumatic Brain Injury: A Multicenter, Randomized, Controlled Trial of Interactive Group Treatment versus Non-Interactive Treatment

Objective To evaluate the effectiveness of a replicable group treatment program for improving social competence after traumatic brain injury (TBI). Design Multicenter randomized controlled trial comparing two methods of conducting a social competency skills program, an interactive group format versus a classroom lecture. Setting Community and Veteran rehabilitation centers. Participants 179 civilian, military, and veteran adults with TBI and social competence difficulties, at least 6 months post-injury. Experimental Intervention Thirteen weekly group interactive sessions (1.5 hours) with structured and facilitated group interactions to improve social competence. Alternative (Control) Intervention Thirteen traditional classroom sessions using the same curriculum with brief supplemental individual sessions but without structured group interaction. Primary Outcome Measure Profile of Pragmatic Impairment in Communication (PPIC), an objective behavioral rating of social communication impairments following TBI. Secondary Outcomes LaTrobe Communication Questionnaire (LCQ), Goal Attainment Scale (GAS), Satisfaction with Life Scale (SWLS), Post-Traumatic Stress Disorder Checklist – (PCL-C), Brief Symptom Inventory 18 (BSI-18), Scale of Perceived Social Self Efficacy (PSSE). Results Social competence goals (GAS) were achieved and maintained for most participants regardless of treatment method. Significant improvements in the primary outcome (PPIC) and two of the secondary outcomes (LCQ and BSI) were seen immediately post-treatment and at 3 months post-treatment in the AT arm only, however these improvements were not significantly different between the GIST and AT arms. Similar trends were observed for PSSE and PCL-C. Conclusions Social competence skills improved for persons with TBI in both treatment conditions. The group interactive format was not found to be a superior method of treatment delivery in this study

CARBON BALANCE AND VEGETATION DYNAMICS IN AN OLD‐GROWTH AMAZONIAN FOREST

Amazon forests could be globally significant sinks or sources for atmospheric carbon dioxide, but carbon balance of these forests remains poorly quantified. We surveyed 19.75 ha along four 1‐km transects of well‐drained old‐growth upland forest in the Tapajós National Forest near Santarém, Pará, Brazil (2°51′ S, 54°58′ W) in order to assess carbon pool sizes, fluxes, and climatic controls on carbon balance. In 1999 there were, on average, 470 live trees per hectare with diameter at breast height (dbh) ≥10 cm. The mean (and 95% ci) aboveground live biomass was 143.7 ± 5.4 Mg C/ha, with an additional 48.0 ± 5.2 Mg C/ha of coarse woody debris (CWD). The increase of live wood biomass after two years was 1.40 ± 0.62 Mg C·ha−1·yr−1, the net result of growth (3.18 ± 0.20 Mg C·ha−1·yr−1 from mean bole increment of 0.36 cm/yr), recruitment of new trees (0.63 ± 0.09 Mg C·ha−1·yr−1, reflecting a notably high stem recruitment rate of 4.8 ± 0.9%), and mortality (−2.41 ± 0.53 Mg C·ha−1·yr−1 from stem death of 1.7% yr−1). The gain in live wood biomass was exceeded by respiration losses from CWD, resulting in an overall estimated net loss from total aboveground biomass of 1.9 ± 1.0 Mg C·ha−1·yr−1. The presence of large CWD pools, high recruitment rate, and net accumulation of small‐tree biomass, suggest that a period of high mortality preceded the initiation of this study, possibly triggered by the strong El Niño Southern Oscillation events of the 1990s. Transfer of carbon between live and dead biomass pools appears to have led to substantial increases in the pool of CWD, causing the observed net carbon release. The data show that biometric studies of tropical forests neglecting CWD are unlikely to accurately determine carbon balance. Furthermore, the hypothesized sequestration flux from CO2 fertilization (\u3c0.5 Mg C·ha−1·yr−1) would be comparatively small and masked for considerable periods by climate‐driven shifts in forest structure and associated carbon balance in tropical forests

Mature neurons dynamically restrict apoptosis via redundant premitochondrial brakes

Apoptotic cell death is critical for the early development of the nervous system, but once the nervous system is established, the apoptotic pathway becomes highly restricted in mature neurons. However, the mechanisms underlying this increased resistance to apoptosis in these mature neurons are not completely understood. We have previously found that members of the miR-29 family of microRNAs (miRNAs) are induced with neuronal maturation and that overexpression of miR-29 was sufficient to restrict apoptosis in neurons. To determine whether endogenous miR-29 alone was responsible for the inhibition of cytochrome c release in mature neurons, we examined the status of the apoptotic pathway in sympathetic neurons deficient for all three miR-29 family members. Unexpectedly, we found that the apoptotic pathway remained largely restricted in miR-29-deficient mature neurons. We therefore probed for additional mechanisms by which mature neurons resist apoptosis. We identify miR-24 as another miRNA that is upregulated in the maturing cerebellum and sympathetic neurons that can act redundantly with miR-29 by targeting a similar repertoire of pro-death BH3-only genes. These results reveal that mature neurons engage redundant brakes to restrict the apoptotic pathway and ensure their long-term survival

Graphics mini manual

The computer graphics capabilities available at the Center are introduced and their use is explained. More specifically, the manual identifies and describes the various graphics software and hardware components, details the interfaces between these components, and provides information concerning the use of these components at LaRC

Toxoplasma gondii Infection Specifically Increases the Levels of Key Host MicroRNAs

The apicomplexan parasite Toxoplasma gondii can infect and replicate in virtually any nucleated cell in many species of warm-blooded animals; thus, it has evolved the ability to exploit well-conserved biological processes common to its diverse hosts. Here we have investigated whether Toxoplasma modulates the levels of host microRNAs (miRNAs) during infection.Using microarray profiling and a combination of conventional molecular approaches we report that Toxoplasma specifically modulates the expression of important host microRNAs during infection. We show that both the primary transcripts for miR-17 approximately 92 and miR-106b approximately 25 and the pivotal miRNAs that are derived from miR-17 approximately 92 display increased abundance in Toxoplasma-infected primary human cells; a Toxoplasma-dependent up-regulation of the miR-17 approximately 92 promoter is at least partly responsible for this increase. The abundance of mature miR-17 family members, which are derived from these two miRNA clusters, remains unchanged in host cells infected with the closely related apicomplexan Neospora caninum; thus, the Toxoplasma-induced increase in their abundance is a highly directed process rather than a general host response to infection.Altered levels of miR-17 approximately 92 and miR-106b approximately 25 are known to play crucial roles in mammalian cell regulation and have been implicated in numerous hyperproliferative diseases although the mechanisms driving their altered expression are unknown. Hence, in addition to the implications of these findings on the host-pathogen interaction, Toxoplasma may represent a powerful probe for understanding the normal mechanisms that regulate the levels of key host miRNAs

Direct Regulation of an Oncogenic Micro-RNA Cluster by E2F Transcription Factors

Micro-RNAs (miRNAs) are a class of non-coding RNAs that post-transcriptionally regulate gene expression via the RNA interference pathway. In addition to roles in normal development, miRNAs have recently been implicated in a range of human diseases, including cancer. We recently demonstrated that a polycistronic cluster of miRNAs, miR-17-92, is oncogenic in a mouse model for Burkitt's lymphoma. This is due, in part, to a reduced apoptotic program. In an effort to understand the regulation of miR-17-92, we have studied the promoter structure of this miRNA cluster. The primary transcript initiates from a consensus initiator sequence downstream of a nonconsensus TATA box. The core promoter region contains two functional E2F transcription factor binding sites. Chromatin immunoprecipitation demonstrates that E2F3 is the primary E2F family member that occupies the promoter. These data place miR-17-92 in a regulatory loop between E2F3 and the miR-17 target E2F1. We propose a model whereby miR-17-92 promotes cell proliferation by shifting the E2F transcriptional balance away from the pro-apoptotic E2F1 and toward the proliferative E2F3 transcriptional network

Mortality following Traumatic Brain Injury among Individuals Unable to Follow Commands at the Time of Rehabilitation Admission: A National Institute on Disability and Rehabilitation Research Traumatic Brain Injury Model Systems Study

Severe traumatic brain injury (TBI) has been associated with increased mortality. This study characterizes long-term mortality, life expectancy, causes of death, and risk factors for death among patients admitted within the National Institute on Disability and Rehabilitation Research (NIDRR) TBI Model Systems Programs (TBIMS) who lack command following at the time of admission for inpatient TBI rehabilitation. Of the 8084 persons enrolled from 1988 and 2009, 387 from 20 centers met study criteria. Individuals with moderate to severe TBI who received inpatient rehabilitation were 2.2 times more likely to die than individuals in the U.S. general population of similar age, gender, and race, with an average life expectancy (LE) reduction of 6.6 years. The subset of individuals who were unable to follow commands on admission to rehabilitation was 6.9 times more likely to die, with an average LE reduction of 12.2 years. Relative to the U.S. general population matched for age, gender, and race/ethnicity, these non–command following individuals were more than four times more likely to die of circulatory conditions, 44 times more likely to die of pneumonia, and 38 times more likely to die of aspiration pneumonia. The subset of individuals with TBI who are unable to follow commands upon admission to inpatient rehabilitation are at a significantly increased risk of death when compared with the U.S. general population and compared with all individuals with moderate to severe TBI receiving inpatient rehabilitation. Respiratory causes of death predominate, compared with the general population